Cost pressures and ever increasing regulatory expectations require new thinking and approaches to development, manufacturing and release of drug substance and product. Efficient changeover between lots, real time disposition and assurance that product quality expectations are met are key features of the future of biologics. Quality by design (QbD) will be a key component of future analytical testing. The QbD paradigm focuses on the physiological importance of quality attributes for molecular design, process development, and control strategies. Analytical methodology will need to evolve and adapt to not only be able to monitor known biologically relevant quality attributes but also to have the flexibility to monitor new attributes as they are discovered without the need to continuously add new methods. A fundamental shift for process development will be to design quality into the product during development and manufacturing rather than relying solely on quality assessment at the end of production. Connecting process understanding with critical quality attributes (CQAs) and preventing issues in real time rather than troubleshooting them afterwards will minimize nonconformance issues and ensure product disposition. As such, the use of process analytical technologies (PAT) will be a key component to commercial manufacturing to monitor and control product quality during the manufacturing process and eliminate final release testing for some attributes.
There is a continuing need to develop methods for improving product quality and/or product analysis. Any improvement that increases product quality and decreases downstream process time can lead to reduced costs associated with manufacturing protein therapeutics. The invention fulfills these needs by providing a simple, effective method of controlling product separation as well as monitoring product quality by providing real time product analysis during biopharmaceutical purification processes thereby improving protein production.